In this project we will explore highly innovative planning and delivery strategies to optimally utilize the powerful dose shaping capabilities of IMPT. The theoretical advantage of proton therapy compared to photon therapy is due to the reduced integral dose (dose bath) and the finite range. The added potential of IMPT compared to IMRT derives from the additional degree of freedom, i.e. the beamlet energy. However, to realize the true potential of IMPT, considerable further research is needed. The specific aims of this project focus on different aspects that influence the power of IMPT: Robust optimization of the dose distributions to reduce their sensitivity to uncertainties, biological dose optimization, personalized treatment optimization, and finally, hypofractionation facilitated via the reduced dose bath achievable with IMPT. This project supports the mission of the NCI to improve the treatment and continuing care of cancer patients.